Related Experiment Video
Updated: May 14, 2026
Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
Quantum-chemistry-guided identification of a dual-functional cod-derived peptide targeting oxidative stress and
Xuan-Ying Xin1, Sungkwon Park2, Hao-Wen Wang1
1Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Jilin Beef Cattle Science and industrial technology major demand collaborative Innovation Center, Department of Animal Science, Yanbian University, Yanji, 133002, China.
Objective:
To identify dual-functional peptides from cod protein targeting oxidative stress and inflammation by investigating their electronic structure-activity relationships through an integrated computational and experimental approach.
Methods:
From 1206 in silico hydrolyzed cod peptides, candidates were screened via dual-target docking (Keap1/TLR4), DFT calculations, and MD simulations, followed by validation in LPS-induced RAW264.7 cells.
Results:
The tetrapeptide YGDF was identified as a lead candidate. In silico analysis predicted that the tetrapeptide YGDF possesses a strong electron-donating propensity due to its unique electronic topology. Fukui function analysis suggested a 'nucleophilic-electrophilic' dual-center distribution, where the Tyr1 site acts as a radical scavenger while the Asp3/Phe4 residues facilitate anchoring within the TLR4 binding pocket. Experimental validation confirmed that YGDF (100 μg/mL) effectively suppressed the NF-κB inflammatory cascade and activated the Nrf2 antioxidant pathway in LPS-induced RAW264.7 cells. Specifically, YGDF inhibited the mRNA expression of iNOS and COX-2 by approximately 75% and 80%, respectively, and induced a 30-fold increase in HO-1 transcription.
Conclusion:
YGDF acts as a dual-target regulator, and its bioactivity is closely associated with the electronic spatial distribution predicted by Fukui function analysis.
